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FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
- Source :
- npj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021), Timbrell, S, Aglan, H, Cramer, A, Foden, P, Weaver, D, Pachter, J, Kilgallon, A, Clarke, R, Farnie, G & Bundred, N 2021, ' FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity ', NPJ Breast Cancer, pp. 65 . https://doi.org/10.1038/s41523-021-00263-3, NPJ Breast Cancer
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
Article
Focal adhesion
03 medical and health sciences
chemistry.chemical_compound
Breast cancer
0302 clinical medicine
Cancer stem cell
Target identification
medicine
Adjuvant therapy
Pharmacology (medical)
Radiology, Nuclear Medicine and imaging
RC254-282
Cancer stem cells
business.industry
Cancer
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
030104 developmental biology
Oncology
Paclitaxel
chemistry
Cell culture
030220 oncology & carcinogenesis
Cancer research
business
Adjuvant
Subjects
Details
- Language :
- English
- ISSN :
- 23744677
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- npj Breast Cancer
- Accession number :
- edsair.doi.dedup.....9faaf4a973faeb3380156a7c27400ffa